Already well known for its groundbreaking effort to rapidly diagnose and treat newborn children with rare, often life-threatening diseases, Rady Children’s Institute for Genomic Medicine (RCIGM) announced it has launched a novel program to evaluate the scalability of new diagnostic and precision medicine that screens for approximately 400 genetic diseases that have available treatment options. Called BeginNGS™ (pronounced “beginnings”), the program has enlisted a Who’s Who of partners in the diagnostic, genetic analysis, and rare disease drug development fields including Alexion, AstraZeneca’s Rare Disease group; Fabric Genomics; Genomemon; Illumina; and TileDB.
The new tool will employ rapid whole-genome sequencing (rWGS) to diagnose genetic diseases and identify potential treatment options for children while they are asymptomatic, a departure from RCIGM’s traditional focus of using rWGS for diagnosing children who are already critically ill. BeginNGS uses a tool called Genome-to-Treatment (GTRx™), to provide treatment guidelines for physicians to help them understand genetic conditions and all treatment options, which could include dietary changes, surgery, medical devices or other interventions, in addition to a list of available approved therapeutics.
RCIGM helped pioneer the use of rWGS for diagnosis of genetic disease in intensive care settings. With the clinical utility of diagnostic rWGS proven, we are using that experience to screen, diagnose, and help treat genetic conditions at or before onset of symptoms,” said Stephen Kingsmore, president an CEO of RCIGM. “We aim to scale newborn sequencing to every life-threatening childhood genetic disease that has an effective treatment.”
Launching the pilot program
Still in its early stages as a pilot program, RCIGM is working to automate genetic sequencing and evaluation with a goal of developing a curated set of 400 disease causing genetic variants that can be used to detect disease. Once it has validated this test, RCIGM will begin enrollment for its evaluation and optimization of BeginNGS, with a goal of testing several thousand newborns and expanding the test to include roughly 500 disorders. While no timetable has been detailed, an RCIGM press release noted that the ultimate goal is to expand the test to including approximately 1,000 genetic disorders and providing rWGS testing to as many as 3.7 million babies annually.
Testing for the genetic diseases will be conducted at rWGS centers from blood-spot sample collected at birth. Positive screening results for the 400 early onset conditions will undergo a confirmatory interpretation before returning results to a physician along with clinical guidance on treatment options.
Building a public-private consortium
To make the most impact as a tool for the diagnosis and treatment of rare diseases, BeginNGS is building a public-private consortium of leading patient advocacy groups and leaders in the biotech and genomics fields. Founding members include rare disease therapeutics developers Alexion, Travere Therapeutics, and Inozyme Pharma.
“Alexion is proud to be a founding member of the RCIGM BeginNGS Consortium to help accelerate newborn screening by whole-genome sequencing,” said Tom Defay, Alexion’s deputy head, Diagnostics Strategy and Development in a press release. “We look forward to continuing our support and providing strategic leadership and technical expertise to advance this technology with the hope of transforming the diagnostic odyssey for patients with genetically-based rare diseases.”
Other collaborators include PlumCare RWE, led by Petros Tsipouras, MD, which will launch a national pilot for WGS in Greece, and LunaPBC which will provide its secure data platform for research collaboration and as well as a platform for engaging parents of children with rare diseases as research partners and to support ongoing care. Luna is uniquely suited to also providing a platform for participation from a broad range of patient advocacy groups, based on its partnership announced in 2019 with the Genetic Alliance that saw the two organizations integrate their respective databases.
The overarching goal of all this work is to supplement existing newborn screening protocols at birthing hospitals throughout the United States with a proven approach that leverages whole-genome sequencing while also increasing the power of newborn screening protocols.
“Expanding rWGS to newborn screening is important work with the potential to end agonizing years-long diagnostic odysseys while yielding critical data on the true prevalence of rare disorders,” said Charlene Son Rigby, CEO of RARE-X, a collaborative platform for global data sharing and analysis to accelerate treatments for rare disease. “Early diagnosis of rare disease patients will also open the door to ongoing monitoring of symptoms and gathering of critical natural history data.”